Effect of Admission Hyperglycemia on Short-Term Prognosis of Patients with Non-ST Elevation Acute Coronary Syndrome without Diabetes Mellitus.

OBJECTIVE: To evaluate the effect of admission hyperglycemia on the short-term prognosis of patients with non-ST elevation acute coronary syndrome (NSTE-ACS) without diabetes mellitus. METHODS: The clinical data of 498 patients with NSTE-ACS admitted to the Department of Cardiology of the First Affiliated Hospital of Henan University of Science and Technology between March 2018 and November 2020 were analyzed. Based on the blood glucose (BG) level at admission, patients were divided into three groups: A (BG < 7.8 mmol/L), B (7.8 mmol/L ≤ BG < 11.1 mmol/L), and C (BG ≥ 11.1 mmol/L). The clinical data of the three groups were compared. RESULTS: There was no significant difference between the three groups in terms of age, sex, hypertension, hyperlipidemia, smoking, and history of myocardial infarction (p > 0.05). However, there were significant differences in the incidences of multivessel disease, renal insufficiency, pump failure, and emergency percutaneous coronary intervention, and levels of high-sensitivity C-reactive protein, cardiac troponin T, and creatine kinase isoenzyme MB among the three groups (p < 0.05 for all). The incidences of severe pump failure, malignant arrhythmias, and death were significantly higher in groups B and C compared to group A (p < 0.05). Additionally, the incidences of severe pump failure, malignant arrhythmias, and death were significantly higher in group C compared to group B (p < 0.05). Multivariate logistic regression analysis showed that hyperglycemia, renal insufficiency, Killip grade III/IV, and age were risk factors of in-hospital death. CONCLUSION: Hyperglycemia at admission is a risk factor for adverse in-hospital clinical outcomes in patients with NSTE-ACS.

Fluorescent Magnetic Iron Oxide NanoparticleEncapsulated Protein Hydrogel Against Doxorubicin-Associated Cardiotoxicity and for Enhanced Cardiomyocyte Survival.

Doxorubicin (DOX) is a widely used and effective anticancer drug. However, it shows high cardiotoxicity in several patients. The exact biological mechanisms of DOX-induced cardiotoxicity remain unclear. In the present study, we developed and assessed novel injectable hydrogel matrices combined with nanoparticles and secretome biomolecules to reduce DOXinduced cytotoxicity in human stem cell-derived cardiomyocytes. A Fe2O3 nanoparticle-loaded biocompatible silk sericin nanocomposite form was fabricated and used as an injectable carrier for secretome for in vivo cardiomyocyte metabolism. The formulated hydrogels carrying secretome were analyzed in vitro for proliferation, migration, and tube formation of human stem cell-derived cardiomyocytes. Biological analyses revealed that the secretome-encapsulated florescent Fe3O2 Silk sericin (Sec@MSS) hydrogel markedly reduced calcein-PI dual staining in cardiomyocytes, revealing significantly induced apoptosis. Furthermore, we evaluated the mitochondrial membrane potential for DOX and Sec@MSS hydrogel, and demonstrated apoptosis of the cardiomyocytes in the DOX-alone and Sec@MSS groups. However, the cardiotoxicity of Sec@MSS sericin was much lower than that in the DOX group, and was further evaluated via VEGFR and TUNEL analyses. The results indicate that Sec@MSS hydrogel might serve as an effective treatment agent in cardiac diseases in the future.

TBC1D25 Regulates Cardiac Remodeling Through TAK1 Signaling Pathway.

Cardiac remodeling is a major early event of heart failure, which is regulated by multiple signaling pathways. Here, we demonstrate that TBC1D25 is upregulated during pathological cardiac remodeling. The aim of this study is to determine the role of TBC1D25 in cardiac remodeling and to illustrate the underlying molecular mechanism. Specifically, cardiac remodeling was induced in TBC1D25-KO mice and their wild-type control mice through partial transverse aortic constriction (TAC) of aortic arch. Knockout TBC1D25 exacerbated cardiac hypertrophy, fibrosis and dysfunction. Meanwhile, TBC1D25 overexpression in both H9C2 cells and NRCMs alleviate Angiotensin II-induced cardiomyocyte hypertrophy in vitro. Moreover, TBC1D25 deficiency increases the phosphorylation levels of TAK1 and its downstream molecular (JNK and p38), whereas overexpressed TBC1D25 inhibits phosphorylation of TAK1, JNK and p38. And TAK1 is the key molecule in this process. Furthermore, we demonstrated that TBC1D25 could directly interacts with TAK1 by immunoprecipitation assay and GST pull-down assay, and the interaction needs the amino acids from at least 138 to 226 in the C-terminal region of TBC1D25 and from 1 to 300 in the C-terminal region of TAK1. We conclude that TBC1D25 suppresses pathological cardiac remodeling via regulating TAK1-JNK/p38 signaling pathway, which suggests that TBC1D25 will likely become a promising therapeutic target for heart failure.

Clinical evaluation of thrombus aspiration combined with tirofiban in patients with acute myocardial infarction with elective percutaneous coronary intervention.

OBJECTIVE: To compare the efficacy and safety of combined treatment with thrombus aspiration and intracoronary tirofiban in patients with acute myocardial infarction (MI), with elective percutaneous coronary intervention (PCI). METHODS: Patients undergoing elective PCI during recovery from acute MI were randomized into two groups; the intervention group received thrombus aspiration and intracoronary tirofiban; the control group received conventional PCI. Baseline clinical characteristics, postoperative coronary blood flow (thrombolysis in myocardial infarction [TIMI] grade), TIMI myocardial perfusion (TMP) grade, no/slow reflow rate and cardiac function (measured by echocardiography 1 month postoperatively) were evaluated. Major adverse cardiac event rate and bleeding complications during surgery (and at 1 month and 1 year postoperatively) were also evaluated. RESULTS: A total of 80 patients were included. Postoperatively, the number of patients with TIMI flow grade 3 and the mean TMP grade were both significantly higher, and the no/slow reflow rate was significantly lower, in the intervention group versus the control group. Echocardiography indicated that cardiac function was significantly improved in the intervention group compared with the control group. There were no major complications in either study group. CONCLUSION: Thrombus aspiration combined with intracoronary tirofiban during recovery from acute MI was effective and relatively well tolerated.

[Effects of docosahexaenoic acid on ion channels of rat coronary artery smooth muscle cells].

OBJECTIVE: To investigate the effects of docosahexaenoic acid (DHA) on large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels and voltage-dependent K(+) (K(V)) channels in rat coronary artery smooth muscle cells (CASMCs), and evaluate the vasorelaxation mechanisms of DHA. METHODS: BK(Ca) and K(V) currents in individual CASMC were recorded by patch-clamp technique in whole-cell configuration. Effects of DHA at various concentrations (0, 10, 20, 40, 60 and 80 µmol/L) on BK(Ca) and K(V) channels were observed. RESULTS: (1) DHA enhanced IBK(Ca) and BK(Ca) tail currents in a concentration-dependent manner while did not affect the stably activated curves of IBK(Ca). IBK(Ca) current densities were (68.2 ± 22.8), (72.4 ± 24.5), (120.4 ± 37.9), (237.5 ± 53.2), (323.6 ± 74.8) and (370.6 ± 88.2)pA/pF respectively (P < 0.05, n = 30) with the addition of 0, 10, 20, 40, 60 and 80 µmol/L DHA concentration, and half-effect concentration (EC(50)) of DHA was (36.22 ± 2.17)µmol/L. (2) IK(V) and K(V) tail currents were gradually reduced, stably activated curves of IK(V) were shift to the right, and stably inactivated curves were shifted to the left in the presence of DHA. IK(V) current densities were (43.9 ± 2.3), (43.8 ± 2.3), (42.9 ± 2.0), (32.3 ± 1.9), (11.7 ± 1.5) and (9.6 ± 1.2)pA/pF respectively(P < 0.05, n = 30)post treatment with 0, 10, 20, 40, 60 and 80 µmol/L DHA under manding potential equal to +50 mV, and EC(50) of DHA was (44.19 ± 0.63)µmol/L. CONCLUSION: DHA can activate BK(Ca) channels and block K(V) channels in rat CASMCs, the combined effects on BK(Ca) and K(V) channels lead to the vasodilation effects of DHA on vascular smooth muscle cells.